Retroviruses are causative agents for many human and animal diseases. They differ from other viruses in that the genetic information of the retrovirus is carried in the viral particle in the form of single-stranded RNA (sense viral RNA) and in the host cells as double-stranded DNA called the provirus. In the case of human and animal lymphotrophic retroviruses, the genome consists of about 9000 bases, including sequences called long terminal repeats (LTR's) of about 700-800 bases at each end of the provirus. Previous studies of human lymphotrophic retroviruses (HTLV-I HTLV-II, and HIV) have identified a number of proteins that are coded directly in the RNA of the various retroviruses.
Retroviral viral particles consist of, in part, envelope (env), group-associated antigens (gag), and reverse transcriptase (pol) proteins together with the RNA genome. Upon infection of a host cell, the reverse transcriptase enzyme uses the sense viral RNA as a template to construct a cDNA molecule (complementary sense DNA; see FIG. 1) complementary to the viral RNA from nucleic acids present in the host cell. The complementary sense DNA molecule is then used as a template by a polymerase to produce a double-stranded DNA, one strand of which corresponds to the original sense viral RNA. This double-stranded DNA copy of the viral RNA (the provirus) then integrates into the host genome and begins to produce viral RNA, mRNA, and proteins. Naturally occurring retroviruses contain all the information required to generate many new retroviral particles from one host cell infection event.
Prior to the present invention, those skilled in the art have only studied the proteins and RNA coded directly by the "sense strand" of the HTLV-I retroviral genome (sense viral RNA and sense mRNA). By identifying open forward reading frames in the sense RNA, many lymphotrophic retroviral proteins have been characterized. We have used this approach to identify proteins coded for on the "anti-sense" mRNA. Moreover, we have detected this anti-sense mRNA and, therefore, proteins encoded by this anti-sense mRNA may be present in HTLV-I infected cells. Further, patients infected with HTLV-I may make antibodies against these anti-sense strand encoded proteins.